The biosynthesis structure and function of the protein chains which comprise the subunits of the keratin intermediate filaments of normal human, murine and bovine epidermis are being investigated. The subunits polymerize in vitro into native-type filaments. The details of filament ultrastructure are being investigated using image analysis procedures of filaments examined by transmission electron microscopic and scanning transmission electron microscopic techniques. Model structures generated from these methods will be computationally tested for compatibility with other physico-chemical data and amino acid sequence studies of individual filament subunits. cDNA cloned probes that encode human and mouse epidermal keratins have been isolated and are being used to determine the amino acid sequences of the proteins, and to study the structure and expression of keratin genes. A histidine-rich basic protein, termed filaggrin, isolated from human epidermis and the slightly different protein of mouse epidermis, specifically aggregate keratin filaments in a manner suggestive of an interfilamentous matrix component. cDNA cloned probes will be isolated to study their structure, expression and amino acid sequence of filaggrin.